1.Production of GTKO pigs and kidney xenotransplantation from pigs to rhesus macaques
Yan WANG ; Yue CHANG ; Chang YANG ; Taiyun WEI ; Xiaoying HUO ; Bowei CHEN ; Jiaoxiang WANG ; Heng ZHAO ; Jianxiong GUO ; Hongfang ZHAO ; Xiong ZHANG ; Feiyan ZHU ; Wenmin CHENG ; Hongye ZHAO ; Kaixiang XU ; Ameen Jamal MUHAMMAD ; Zhendi WANG ; Hongjiang WEI
Organ Transplantation 2025;16(4):526-537
		                        		
		                        			
		                        			Objective To explore the construction of α-1,3-galactosyltransferase (GGTA1) gene-knockout (GTKO) Diannan miniature pigs and the kidney xenotransplantation from pigs to rhesus macaques, and to assess the effectiveness of GTKO pigs. Methods The GTKO Diannan miniature pigs were constructed using the CRISPR/Cas9 gene-editing system and somatic cell cloning technology. The phenotype of GTKO pigs was verified through polymerase chain reaction, Sanger sequencing and immunofluorescence staining. Flow cytometry was used to detect antigen-antibody (IgM) binding and complement-dependent cytotoxicity. Kidney xenotransplantation was performed from GTKO pigs to rhesus macaques. The humoral immunity, cellular immunity, coagulation and physiological indicators of the recipient monkeys were monitored. The function and pathological changes of the transplanted kidneys were analyzed using ultrasonography, hematoxylin-eosin staining, immunohistochemical staining and immunofluorescence staining. Results Single-guide RNA (sgRNA) targeting exon 4 of the GGTA1 gene in Diannan miniature pigs was designed. The pGL3-GGTA1-sgRNA1-GFP vector was transfected into fetal fibroblasts of Diannan miniature pigs. After puromycin selection, two cell clones, C59# and C89#, were identified as GGTA1 gene-knockout clones. These clones were expanded to form cell lines, which were used as donor cells for somatic cell nuclear transfer. The reconstructed embryos were transferred into the oviducts of trihybrid surrogate sows, resulting in 13 fetal pigs. Among them, fetuses F04 and F11 exhibited biallelic mutations in the GGTA1 gene, and F04 had a normal karyotype. Using this GTKO fetal pig for recloning and transferring the reconstructed embryos into the oviducts of trihybrid surrogate sows, seven surviving piglets were obtained, all of which did not express α-Gal epitope. The binding of IgM from the serum of rhesus monkey 20# to GTKO pig PBMC was reduced, and the survival rate of GTKO pig PBMC in the complement-dependent cytotoxicity assay was higher than that of wild-type pig. GTKO pig kidneys were harvested and perfused until completely white. After the left kidney of the recipient monkey was removed, the pig kidney was heterotopically transplanted. Following vascular anastomosis and blood flow restoration, the pig kidney rapidly turned pink without hyperacute rejection (HAR). Urine appeared in the ureter 6 minutes later, indicating successful kidney transplantation. The right kidney of the recipient was then removed. Seven days after transplantation, the transplanted kidney had good blood flow, the recipient monkey's serum creatinine level was stable, and serum potassium and cystatin C levels were effectively controlled, although they increased 10 days after transplantation. Seven days after transplantation, the levels of white blood cells, lymphocytes, monocytes and eosinophils in the recipient monkey increased, while platelet count and fibrinogen levels decreased. The activated partial thromboplastin time, thrombin time and prothrombin time remained relatively stable but later showed an upward trend. The recipient monkey survived for 10 days. At autopsy, the transplanted kidney was found to be congested, swollen and necrotic, with a small amount of IgG deposition in the renal tissue, and a large amount of IgM, complement C3c and C4d deposition, as well as CD68+ macrophage infiltration. Conclusions The kidneys of GTKO Diannan miniature pigs may maintain normal renal function for a certain period in rhesus macaques and effectively overcome HAR, confirming the effectiveness of GTKO pigs for xenotransplantation.
		                        		
		                        		
		                        		
		                        	
2.Historical Evolution and Key Information Research on Pediatric Famous Classical Formula Yigongsan
Jiangmin SU ; Jun ZHANG ; Cong GUO ; Anyi ZHAO ; Liang JIANG ; Heng ZHANG ; Jipeng DI ; Sha CHEN ; Li LIU ; Yan LIU ; An LIU
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(7):205-214
		                        		
		                        			
		                        			Yigongsan is derived from Xiaoer Yaozheng Zhijue written by QIAN Yi in the Northern Song dynasty, which is the No. 3 formula in the Catalogue of Ancient Famous Classical Formulas(The Second Batch of Pediatrics) released by the National Administration of Traditional Chinese Medicine(TCM) in September 2022, and it can be developed as a class 3.1 new TCM drug. By referring to ancient medical books and modern literature, this study conducted herbal textual research on Yigongsan from five aspects, including historical evolution, origin and processing, dosage conversion, usage and preparation methods, and functional application, then formed the key information table of this formula, in order to provide reference for the development of reference samples and preparations of Yigongsan. Based on the results of the study, it is recommended that Panax ginseng should be removed the basal part of stem(rhizoma), Poria cocos should be removed the peel, Citrus reticulata should be cut into shreds and Glycyrrhiza uralensis should be used. According to 4.13 g/Qian(钱), 1 g/slice for ginger, 3 g for each jujube and 300 mL/Zhan(盏), the doses of Ginseng Radix, Poria, Atractylodis Macrocephalae Rhizoma, Glycyrrhizae Radix et Rhizoma, Citri Reticulatae Pericarpium, Zingiberis Rhizoma Recens, Jujubae Fructus were 1.652, 1.652, 1.652, 1.652, 1.652, 5, 6 g, and the total amount was 19.26 g. The decocting method was to crush the medicinal materials into fine powder with 50-80 mesh, add 300 mL of water and decoct to 210 mL for each dose, then remove the dregs and take it warmly. This formula was recorded in ancient books as the main treatment for the cold-deficiency of spleen and stomach, and Qi stagnation in children with vomiting and diarrhea and lack of appetite. It has been flexibly applied by later generations of physicians, and is often used to treat anorexia, inflammation of the digestive tract, diarrhea and other diseases in children. 
		                        		
		                        		
		                        		
		                        	
3.Nutritional status and its related factors among primary and secondary school students in Beijing City
WANG Yan, SUN Bingjie, ZHAO Hai, XU Huiyu, GAO Ruoyi, LUO Huijuan, GUO Xin
Chinese Journal of School Health 2024;45(2):188-192
		                        		
		                        			Objective:
		                        			To assess the nutritional status of primary and secondary school students in Beijing City and to analyze the related factors, so as to provide a scientific basis for improving the nutritional status of primary and secondary school students in a targeted manner.
		                        		
		                        			Methods:
		                        			Based on the 2021 Beijing Student Common Diseases and Health Influencing Factors Surveillance Project, a stratified random cluster sampling method was used to conduct a physical examination and questionnaire survey on 25 487 primary and secondary school students from September to November 2021. The  Chi square test was used for comparison of nutritional status detection rates, and disordered multi classification Logistic regression analysis was used to explore the factors associated with students  nutritional status.
		                        		
		                        			Results:
		                        			The detection rates of malnutrition, overweight and obesity among primary and secondary school students in Beijing City were 4.7%, 18.0% and 23.8% respectively. The detection rates of malnutrition, overweight and obesity were higher among male students (5.1%, 20.4%, 29.7%) than female students (4.2%, 15.5%, 17.4%) ( χ 2= 12.23, 101.71, 526.99,  P <0.01). The detection rate of obesity was higher in the suburbs than urban areas(26.6%, 19.8%), and the detection rate of malnutrition was lower in the suburbs than urban areas (4.2%,5.5%)( χ 2=157.25, 23.61,  P <0.01). The results of disordered multi classification Logistic regression showed that the related factors for malnutrition, overweight and obesity were gender, residence, moderate to vigorous exercise ≥60 min per day and lack of sleep( OR =1.70, 1.88,2.48; 1.14, 0.87, 0.67; 0.85, 0.92,  0.81 ; 0.83, 1.08, 1.07); frequency of fried food intake daily was a related factor for overweight ( OR =0.70); whether eating breakfast daily or not was a related factor for overweight and obesity ( OR =0.91, 0.84); academic level (middle and high school) was a related factor for malnutrition and obesity ( OR =1.38, 1.37; 0.77, 1.40)( P <0.05).
		                        		
		                        			Conclusions
		                        			The problem of overweight and obesity among primary and secondary school students in Beijing City continues to be serious, especially among boys and suburban areas. It is recommended that society, schools, families and individuals should work together to improve the nutritional status of primary and secondary school students by adopting a graded and classified approach.
		                        		
		                        		
		                        		
		                        	
4.Improvement effects of 3,5,6,7,8,3′,4′-heptamethoxyflavone of Fructus Aurantii on rats with damp blockage of the middle energizer
Wenhui GONG ; Yating XIE ; Li XIN ; Shihao YAN ; Beibei ZHAO ; Yuqing ZHENG ; Jingying GUO ; Jie SHANG ; Peng ZHENG ; Jinlian ZHANG
China Pharmacy 2024;35(7):819-824
		                        		
		                        			
		                        			OBJECTIVE To investigate the improvement effects of 3,5,6,7,8,3′,4′-heptamethoxyflavone (HMF) of Fructus Aurantii on rats with damp blockage of the middle energizer. METHODS The rats were randomly divided into normal group, model group, positive control group (Raceanisodamine tablet, 1 mg/kg), HMF low-dose, medium-dose and high-dose groups (0.3, 0.6, 0.9 mg/kg), with 7 rats in each group. Except for the normal group, the other groups were modeled by internal and external composite factors. After successful modeling, the rats in each group were given the corresponding drug or normal saline, once a day, for 14 days. The general behavioral states such as dietary intake, water intake and mental state of the rats were observed, and the fecal water content rate and saliva flow rate were measured. Hematoxylin-eosin (HE) staining was used to observe the pathological and morphology in gastric and small intestinal tissues of rats. The plasma content of aldosterone was detected, and the expression of aquaporins (AQP3) in the gastric tissue of rats was determined. RESULTS Compared with the normal group, the dietary intake and water intake of the model group rats were significantly decreased (P<0.01), the fecal water content rate, salivary flow rate, plasma content of aldosterone and the expression of AQP3 in gastric tissue were increased significantly (P<0.01). Gastric tissue injury invaded the mucosal muscle layer, resulting in mucosal muscle layer rupture; pathological and morphological changes such as small intestinal villous erosion and glandular structure destruction were observed in the small intestine. Compared with the model group, the dietary intake and water intake of rats were increased in HMF groups; fecal water content rate, salivary flow rate, plasma content of aldosterone, the expression of AQP3 in gastric tissue were decreased, most of the above differences were statistically significant (P<0.05 or P<0.01). The pathological and morphological changes in the gastric and small intestine tissues of rats had been improved to varying degrees. CONCLUSIONS HMF of Fructus Aurantii with dry property HMF could improve the symptoms of rats with damp blockage of middle energizer, the mechanism of which may be associated with reducing the content of plasma aldosterone and down-regulating the expression of gastric AQP3.
		                        		
		                        		
		                        		
		                        	
5.Bionic design,preparation and clinical translation of oral hard tissue restorative materials
Han ZHAO ; Yan WEI ; Xuehui ZHANG ; Xiaoping YANG ; Qing CAI ; Chengyun NING ; Mingming XU ; Wenwen LIU ; Ying HUANG ; Ying HE ; Yaru GUO ; Shengjie JIANG ; Yunyang BAI ; Yujia WU ; Yusi GUO ; Xiaona ZHENG ; Wenjing LI ; Xuliang DENG
Journal of Peking University(Health Sciences) 2024;56(1):4-8
		                        		
		                        			
		                        			Oral diseases concern almost every individual and are a serious health risk to the popula-tion.The restorative treatment of tooth and jaw defects is an important means to achieve oral function and support the appearance of the contour.Based on the principle of"learning from the nature",Deng Xu-liang's group of Peking University School and Hospital of Stomatology has proposed a new concept of"microstructural biomimetic design and tissue adaptation of tooth/jaw materials"to address the worldwide problems of difficulty in treating dentine hypersensitivity,poor prognosis of restoration of tooth defects,and vertical bone augmentation of alveolar bone after tooth loss.The group has broken through the bottle-neck of multi-stage biomimetic technology from the design of microscopic features to the enhancement of macroscopic effects,and invented key technologies such as crystalline/amorphous multi-level assembly,ion-transportation blocking,and multi-physical properties of the micro-environment reconstruction,etc.The group also pioneered the cationic-hydrogel desensitizer,digital stump and core integrated restora-tions,and developed new crown and bridge restorative materials,gradient functionalisation guided tissue regeneration membrane,and electrically responsive alveolar bone augmentation restorative membranes,etc.These products have established new clinical strategies for tooth/jaw defect repair and achieved inno-vative results.In conclusion,the research results of our group have strongly supported the theoretical im-provement of stomatology,developed the technical system of oral hard tissue restoration,innovated the clinical treatment strategy,and led the progress of the stomatology industry.
		                        		
		                        		
		                        		
		                        	
6.Nutlin-3a regulates mouse adipose function by inhibition of CIDEC expression
Enhui CHEN ; Jiahui YANG ; Wei ZHAO ; Xianghong XIE ; Yanfang GUO ; Xiaojun LIU ; Li YAN
Basic & Clinical Medicine 2024;44(2):154-158
		                        		
		                        			
		                        			Objective To investigate the effect of Nutlin-3a,a mouse double minute 2 homolog(MDM2)inhibitor,on lipid metabolism of mouse adipose.Methods High-fat diet-induced obesity(DIO)C57BL/6J mice were randomly divided into a control group injected with DMSO and an experimental group injected with Nutlin-3a.Then we conducted glucose tolerance(GTT)and insulin tolerance(ITT)tests.The epididymal white adipose tissue(eWAT),inguinal white adipose tissue(iWAT)and brown adipose tissue(BAT)of animals were isolated and microscopy of WATs with hematoxylin-eosin(HE)staining was performed to observe the morphological changes of adipocytes.The expression of lipid metabolism related gene cell death-inducing DFF45-like effector C(CIDEC)in eWAT were detected by qPCR and Western blot.Results Compared with the control group,Nutlin-3a was found to promote the body weight(P<0.001),but no effect on glucose tolerance and insulin sensitivity in DIO mice.Nutlin-3a treatment decreased the size of adipocytes and fat deposition in adipose tissue and downregulated the mRNA and protein levels of CIDEC in eWAT.Conclusions Nutlin-3a inhibits the formation of lipid droplets by downregulating expression of CIDEC in white adipose tissue.
		                        		
		                        		
		                        		
		                        	
7.Clinical efficacy analysis of interventional treatment of iatrogenic massive vaginal bleeding
Shengdong QIN ; Chaodi LI ; Yuhong HOU ; Yanping ZHAO ; Su YAN ; Ruixia GUO ; Xinwei HAN ; Jianhao ZHANG
Journal of Practical Radiology 2024;40(1):103-106
		                        		
		                        			
		                        			Objective To investigate the clinical efficacy and value of interventional treatment of iatrogenic massive vaginal bleed-ing.Methods Retrospective analysis was performed on 35 patients with postoperative vaginal massive hemorrhage in obstetrics and gynecology who were admitted.Abdominal aorta and bilateral internal iliac arteries angiography and embolization of abnormal vessels were performed under digital subtraction angiography(DS A),and relevant clinical data were recorded and analyzed.Results After interventional treatment,the vaginal bleeding of 33 patients basically stopped within 3 days,and the average interventional operation time was(57.5±17.2)min.The hemoglobin value,hematocrit and blood pressure decreased and the heart rate increased significantly before and after interventional embolization in obstetrics and gynecology,with statistical significance(P<0.05).There were no sig-nificant changes in hemoglobin value and hematocrit between the completion of interventional embolization and 72 hours after interventional embolization(P>0.05).The increase of blood pressure and the decrease of heart rate were statistically significant(P<0.05).Two patients with cesarean section had poor hemostatic effect after interventional embolization,and the bleeding stopped after exploratory laparotomy and hysterectomy.Conclusion Interventional treatment has the advantages of small trauma,simple operation,signifi-cant curative effect,few adverse reactions,and rapid recovery.It plays an important role and clinical value in the diagnosis and treat-ment of iatrogenic vaginal bleeding.
		                        		
		                        		
		                        		
		                        	
8.Investigation on major cognition and major choice motivation of medical freshmen
Lizhi LÜ ; Huangda GUO ; Xiaowen LIU ; Lin XU ; Yuxuan ZHAO ; Yan WANG ; Yawen JIA ; Yun WANG
Chinese Journal of Medical Education Research 2024;23(3):353-358
		                        		
		                        			
		                        			Objective:To understand the major cognition, major choice motivation and the relationship between the two of medical students, and provide references and suggestions for the selection of talents in various majors of medical schools and the effective development of enrollment work.Methods:This study selected undergraduates of Batch 2019 from Peking University Health Science Center as the survey objects, conducted a questionnaire survey on their major cognition, major choice motivation and influencing factors, and used principal component analysis and Spearman rank correlation analysis.Results:The study found that the major cognition scores of 640 undergraduates of Batch 2019 from Peking University Health Science Center were clinical medicine (3.24±0.89) > stomatology (2.89±1.00) > basic medicine (2.66±1.02) > pharmacy (2.54±0.97) > preventive medicine (2.29±0.93) > nursing medicine (2.21±0.99) > medical laboratory (1.98±0.95) > medical English (1.95±0.93). Six major motivation factors for professional choice were school and professional strength, professional learning and job prospects, own factors, Peking University sentiments and the influence of others, medical factors, school policies, and the contribution rates were 34.60%, 12.97%, 7.42%, 6.00%, 5.59% and 5.37%, respectively. Major cognition scores and major choice motivation factors were positively correlated with each other to some extent.Conclusions:At present, students' major cognition level of medical majors still has a large room for improvement, and the motivational factors of major choice are more complicated, among which "the school and professional strength" and "the prospects of study and work" are important factors. Medical schools should focus on strengthening major publicity, improving students' major cognition, attracting aspiring students to apply for medical majors from many aspects, and improving the training quality of medical professionals.
		                        		
		                        		
		                        		
		                        	
9.Clinical guidelines for the treatment of ankylosing spondylitis combined with lower cervical fracture in adults (version 2024)
Qingde WANG ; Yuan HE ; Bohua CHEN ; Tongwei CHU ; Jinpeng DU ; Jian DONG ; Haoyu FENG ; Shunwu FAN ; Shiqing FENG ; Yanzheng GAO ; Zhong GUAN ; Hua GUO ; Yong HAI ; Lijun HE ; Dianming JIANG ; Jianyuan JIANG ; Bin LIN ; Bin LIU ; Baoge LIU ; Chunde LI ; Fang LI ; Feng LI ; Guohua LYU ; Li LI ; Qi LIAO ; Weishi LI ; Xiaoguang LIU ; Hongjian LIU ; Yong LIU ; Zhongjun LIU ; Shibao LU ; Yong QIU ; Limin RONG ; Yong SHEN ; Huiyong SHEN ; Jun SHU ; Yueming SONG ; Tiansheng SUN ; Yan WANG ; Zhe WANG ; Zheng WANG ; Hong XIA ; Guoyong YIN ; Jinglong YAN ; Wen YUAN ; Zhaoming YE ; Jie ZHAO ; Jianguo ZHANG ; Yue ZHU ; Yingjie ZHOU ; Zhongmin ZHANG ; Wei MEI ; Dingjun HAO ; Baorong HE
Chinese Journal of Trauma 2024;40(2):97-106
		                        		
		                        			
		                        			Ankylosing spondylitis (AS) combined with lower cervical fracture is often categorized into unstable fracture, with a high incidence of neurological injury and a high rate of disability and morbidity. As factors such as shoulder occlusion may affect the accuracy of X-ray imaging diagnosis, it is often easily misdiagnosed at the primary diagnosis. Non-operative treatment has complications such as bone nonunion and the possibility of secondary neurological damage, while the timing, access and choice of surgical treatment are still controversial. Currently, there are no clinical practice guidelines for the treatment of AS combined with lower cervical fracture with or without dislocation. To this end, the Spinal Trauma Group of Orthopedics Branch of Chinese Medical Doctor Association organized experts to formulate Clinical guidelines for the treatment of ankylosing spondylitis combined with lower cervical fracture in adults ( version 2024) in accordance with the principles of evidence-based medicine, scientificity and practicality, in which 11 recommendations were put forward in terms of the diagnosis, imaging evaluation, typing and treatment, etc, to provide guidance for the diagnosis and treatment of AS combined with lower cervical fracture.
		                        		
		                        		
		                        		
		                        	
10.Role of Ferroptosis in Osteoarthritis and Traditional Chinese Medicine Intervention: A Review
Xiaojing GUO ; Huan QIN ; Dongliang XIANG ; Yan WANG ; Li ZHANG ; Bo ZHANG ; Shujin WANG ; Xiaotong LI ; Mingyue ZHAO ; Shanhong WU ; Fei PEI
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(19):263-272
		                        		
		                        			
		                        			Osteoarthritis (OA) is characterized by articular cartilage degeneration, synovial hyperplasia, hyperosteogeny, and narrowing of joint space, which can be caused by trauma, inflammation, and other factors. With the increasing global population aging, the incidence of OA is rising year by year, making it a major public health problem that urgently needs to be addressed. Exploring effective treatment schemes is particularly important. The pathogenesis of OA is complex, including oxidative stress, autophagy, and apoptosis. Recent studies have found that ferroptosis, a new type of cell death, is also an important pathogenic factor in OA, characterized by a series of complex changes such as iron ion accumulation, glutathione (GSH) depletion, and mitochondrial dysfunction. Research shows that inhibiting ferroptosis in chondrocytes can promote chondrocyte proliferation, delay extracellular matrix (ECM) degradation, and reduce synovial hyperplasia and inflammation. Targeting ferroptosis is a new direction in the treatment of OA. OA treatment includes intra-articular injections of steroids or hyaluronic acid and artificial joint replacement, but there are limitations. Traditional Chinese medicine (TCM) has been widely used in the treatment of various diseases because of its low cost, low drug resistance, and few side effects. Cell and animal experiments have further confirmed that TCM can intervene in the treatment of OA with ferroptosis from multiple targets, multiple levels, and aspects, but the mechanism of its treatment of OA based on ferroptosis has not been clarified. This paper discussed iron metabolism, lipid peroxidation, cysteine/glutamate transporter system Xc- (system Xc-)/GSH/glutathione peroxidase 4 (GPX4) pathway, nicotinamide adenine dinucleotide phosphate(NADPH)/ferroptosis suppressor protein 1 (FSP1)/coenzyme Q10 (CoQ10) pathway, tumor protein p53 in OA, and related molecular targets of Chinese medicine monomers and compounds on ferroptosis inhibition. Their potential therapeutic mechanisms were further analyzed to provide theoretical guidance for the treatment of OA by TCM and useful reference for the research and development of related drugs. 
		                        		
		                        		
		                        		
		                        	
            

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